Background: Gastroparesis is a condition of delayed gastric emptying with symptoms of early satiety, nausea and vomiting. It occurs in patients with long-standing diabetes mellitus and after upper GI surgery, especially vagotomy; it is idiopathic in many patients. Interstitial cells of Cajal (ICC) are the electrical pacemaker cells of the GI tract; they occur in the inner circular and outer longitudinal muscle layers, and in the intermyenteric plexus. Patients with gastroparesis may have dysfunction or paucity of innervation and/or ICC that may contribute to the pathophysiology, symptoms and treatment outcomes. One therapy for patients with gastroparesis is the placement of an electrical stimulator in the gastric wall.Design: The aim of this study was to evaluate gastric ICC and enteric innervation in patients with gastroparesis and to determine if these influence treatment outcomes with gastric electric stimulation (GES). Full thickness gastric specimens were obtained in patients undergoing surgical placement of a gastric electric stimulator. H+E stains, as well as immunohistochemistry with Neuron Specific Enolase for ganglion cells and c-Kit for ICC were evaluated. Patients were followed and classified as responders or non-responders to GES using the modified Clinical Patient Grading Assessment Scale (CPGAS).Results: 74 patients with refractory gastroparesis (35 diabetic, 35 idiopathic, 4 post Nissen) underwent implantation of a gastric electric stimulator from July 2010 to November 2011. Of the 66 patients who had full thickness specimens, 47 improved with GES whereas 19 patients stayed the same or worsened. ICC were decreased in each layer in patients who did not improve with GES compared to those who improved: ICC/hpf in outer longitudinal muscle layer (0.82±0.11 vs 1.42±0.15; p=0.002); inner circular muscle layer (2.20±0.19 vs 2.86±1.49; p=0.028); and myenteric plexus (0.91±0.16 vs 1.02±0.09; p=0.54). The CPGAS improvement score at follow-up (average 6.5 months) correlated with the number of ICC in the outer longitudinal muscle layer (r=0.272; p=0.003), the inner circular muscle layer (r=0.210; p=0.021), and myenteric plexus (r=0.181; p=0.057). The number of ganglion cells and number of ganglia were similar in responders and nonresponders.Conclusions: Gastroparetic patients who do not respond to GES had fewer ICC than patients who improved. Information from gastric full thickness biopsies may provide prognostic information on outcome of GES treatment for gastroparesis.Category: Gastrointestinal